AB0070 PIM KYNASES AS POSSIBLE THERAPEUTIC TARGETS IN INFLAMMARORY ARTHRITIDES
Authors: E. Assirelli, J. Ciaffi, S. Naldi, V. Scorcu, L. Mancarella, V. Brusi, L. Lisi, F. Ursini, S. Neri
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Proviral integration site for Moloney murine leukemia virus (PIM) 1 kinase and its family members (PIM2 and PIM3) regulate several cellular functions including survival, proliferation and apoptosis. These proteins have been extensively studied in tumorigenesis, whereas their role in autoimmune and chronic inflammatory diseases remain unclear. PIM kinases are involved in T-cell amplification and differentiation in inflammatory Th1 and Th17 effector T cells subsets. Recent studies suggest that the expression of PIM1 is upregulated in fibroblast-like synoviocytes and CD4+ T cells from patients with rheumatoid arthritis (RA). However, data are lacking regarding the potential role of PIM kinases in spondyloarthritis (SpA) such as psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA). <h3>Objectives</h3> To explore the potential role of PIM kinases in inflammatory arthritides, we evaluated PIM kinases expression at gene and protein level in patients with RA, PsA, and AxSpA compared to healthy controls (CTR). <h3>Methods</h3> PIMs expression was analysed in 26 (11 RA, 7 AxSpA, and 8 PsA) biologic DMARDs (bDMARDs)-naive arthritis patients and 13 controls. PIMs mRNA levels were determined in total RNA extracted from freshly isolated peripheral blood mononuclear cells (PBMC) by real-time semi-quantitative PCR. Protein levels were quantified in serum by ELISA test. Data were analysed by Kruskal Wallis test followed by Dunn's correction for multiple comparisons. <h3>Results</h3> All the samples showed expression of PIM1, 2, and 3 kinases both at gene and protein level, with PIM 3 being the less expressed protein. A trend towards lower expression of PIM1 was appreciated in AxSpA samples compared to other groups, reaching statistical significance only for serum protein levels compared to controls (p &lt; 0.05). No significant differences were found in PIM2 and PIM3 expression, although all arthritis patients showed a trend towards higher serum levels compared to controls, not mirrored at gene expression levels. <h3>Conclusion</h3> PIM 1 mRNA expression in PBMCs seems to mirror PIM1 protein expression in the serum in all groups, supporting this molecule as a candidate biomarker. Controls, RA and PsA patients displayed similar levels, whereas AxSpA patients showed a trend towards reduced PIM1 levels deserving further investigation. Conversely, serum PIM2 and PIM3 levels did not mirror PIM2 and PIM3 gene expression in resting PBMC. Unlike PIM1, the expression of PIM2 and PIM3 have never been studied in PsA and AS, and additional data are required to explore the potential relevance of PIM2 and PIM3 in SpA pathophysiology. Further studies are also required to evaluate PIM kinases modulation after in vitro cell stimulation, the differential expression in PBMC subpopulations, and the impact of disease activity and concurrent disease-modifying medications. <h3>References</h3> [1]Y-J Ha et al., Rheumatol. 2019;58:154-64; [2]N J Maney et al. Arthritis &amp; Rheumatol. 2021; 73: 1820-30. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.